Gamma radiation-based imaging techniques employ tracer compounds that are introduced into the body to be imaged. The tracer compounds contain a radionuclide which directly or indirectly releases photons whose locations of origin within the body are then calculated from intercept data gathered by gamma radiation detectors. Two commonly employed gamma radiation-based imaging techniques are Positron Emission Tomography (referred to as PET) and Single Photon Emission Computed Tomography (referred to as SPECT). In PET, the radionuclide indirectly releases a pair of oppositely directed photons. The PET radionuclide emits a positron, which upon contact with an electron in its immediate vicinity triggers anti-matter annihilation of both particles which event emits the pair of photons. In SPECT, the radionuclide is a direct gamma emitter. Examples of isotopes useful in gamma radiation-based imaging include Carbon-11 (referred to as 11C or C11), Fluorine-18 (referred to as 18F or F18), Technetium-99m (referred to as 99mTc or Tc99m), Indium-111 (referred to as 111In or In111) and Iodine-123 (referred to as 123I or I123).
In addition to the radionuclide, the tracer compound comprises a ligand which provides an affinity of the tracer to a selected target associated with one or more tissues, organs or conditions of interest.
Among the 11 phosphodiesterase (PDE) families, only PDE1 is calcium and calmodulin activated. Under chronic stress conditions of increased intracellular calcium, therefore, this system is most relevant. The chronic increase in intracellular calcium is well established in hypertension. PDE1 is a family of three sub-types PDE1-A, B, and C. PDE1B is primarily located in the brain. PDE1A is expressed in brain and sperm. PDE1C is enriched in arterial smooth muscle cells, myocardium and atherosclerotic lesions as well as other tissues. There is increasing evidence of a linkage of PDE1C and smooth muscle proliferation and in cardiac hypertrophy associated with heart disease. Until recently the state of the art in the PDE1 field had not progressed to produce suitable-selective and potent inhibitors. The inhibitors used in the literature are known to be very unselective. The fact that PDE1 is capable of hydrolysis of both cAMP and cGMP is another positive aspect that would indicate beneficial effects on both smooth muscle cell proliferation and on pulmonary vascular hypertension. PDE1-specific drug candidates have been developed including several series of agents with nanomolar potencies and remarkable specificities.